AzTrials
AzTrials

CirrhosisPhase 2NCT05014594

Sodium-glucose Linked Transporter 2 (SGLT-2) Inhibitors in Recurrent Ascites: a Pilot RCT

A Phase 2 study testing Dapagliflozin (10Mg Tab) along with standard medical therapy in people with Cirrhosis and Ascites Hepatic, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

The development of ascites is a landmark event in the natural history of cirrhosis and signifies a grim prognosis. Portal hypertension and splanchnic arterial vasodilatation are the major contributors in the development of ascites. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Cirrhosis, Ascites Hepatic
What is being tested?
Dapagliflozin (10Mg Tab) along with standard medical therapy
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
44 participants
Where
1 siteIndia
Study dates
3 Sep 2021to 19 May 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18-70 years
  • Cirrhosis as determined by clinical findings, hemogram and liver function tests, endoscopic findings and imaging
  • Recurrent ascites: Recurrent ascites will be defined as tense ascites recurring at least thrice within the last 1-year despite optimal standard medical treatment including large volume paracentesis and diuretics

Who cannot join

  • Presence of chronic kidney disease as defined by an estimated glomerular filtration rate of <60 ml/min for more than 3 months. The MDRD-6 equation will be used for estimating GFR.
  • Portal vein thrombosis
  • Hepatocellular carcinoma.
  • Gastrointestinal bleed in the preceding 2-weeks
  • Overt hepatic encephalopathy in the preceding 1-month
  • Documented hypoglycemia in the preceding 1-month
Show all 18Show fewer
  • Serum sodium < 125 meq/l
  • History of skeletal fracture in the preceding year or any past history of fragility fracture
  • History of peripheral vascular disease
  • Acute kidney injury as defined by the International Club of Ascites criteria
  • Infection within 1-month preceding the study
  • Anatomic urologic defects that predispose to urinary tract infection
  • Mixed ascites (additional etiology of ascites apart from portal hypertension)
  • Any severe extra hepatic condition including respiratory and cardiac failure
  • Acute-on-chronic liver failure as per the APASL or CANONIC criteria
  • Treatment with drug with known effects on systemic and renal hemodynamics within 7 days of inclusion excepting beta-blockers
  • Patients opting for liver transplant or TIPS
  • Refusal to give consent

Trial locations and contacts

1 site in 1 country.

Virendra Singh, MD,DM,FASGE contact

0172-275-6338

virendrasingh100@hotmail.com

Rishav Aggarwal, MBBS contact

9914032190

rishavaggarwal90@gmail.com

India1 site, 1 recruiting

  • Dept of Hepatology, PGIMER

    Chandigarh, 160012

    Virendra Singh, MD, DM, +911722756338, virendrasingh100@hotmail.com

    Recruiting

Other trials in India

About this study

The development of ascites is a landmark event in the natural history of cirrhosis and signifies a grim prognosis. Portal hypertension and splanchnic arterial vasodilatation are the major contributors in the development of ascites. Vasodilatation with the consequential decrease in effective circulating volume leads to the activation of sympathetic nervous system and renin angiotensin aldosterone system (RAAS), leading to antinatriuretic effects and retention of sodium and water. This results in the formation of ascites. Management of ascites primarily consists of salt restrictrion and diuretics. Liver transplant is the ultimate panacea.

Dapaglifozin, a Sodium glucose linked transporter-2(SGLT-2) inhibitor, is a part of the routine armamentarium for treatment of patients with Diabetes Mellitus type-2. Its safety is well established in non-diabetic patients too where it has been shown to improve cardiovascular outcomes. The risk of hypoglycemia is negligible as its action is independent of insulin. By virtue of its natriuretic effect, it has been shown to reduce hospitalisations in patients with heart failure irrespective of the presence of diabetes. We hypothesise that a similar natriuretic effect may help in suppressing the renin-angiotensin axis with improved mobilization of ascites in patients with cirrhosis. Pharmacokinetic data on the use of Dapaglifozin suggest that there is no need for dose modification in cirrhosis. The AUC and Cmax for Dapaglifozin in Child Pugh C cirrhosis is 67% and 40%, respectively. In a recent small case series, SGLT-2 inhibitors including dapaglifozin led to improvement in fluid retention and serum sodium, without acute kidney injury or encephalopathy, in patients with cirrhosis. However, SGLT-2 inhibitors have not been evaluated in randomized controlled trials. In this pilot study, we plan to evaluate the efficacy and safety of dapaglifozin in cirrhotics patients with recurrent ascites.

Being tested
Dapagliflozin (10Mg Tab) along with standard medical therapy, Placebo of dapaglifozin along with standard medical therapy
Medical subject headings
Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dapagliflozin (10Mg Tab) along with standard medical therapyDrug

    Oral Dapaglifozin (10 mg/day) along with standard medical therapy will be given to Group A while a placebo of dapaglifozin along with standard medical therapy will be used in Group B

  • Placebo of dapaglifozin along with standard medical therapyDrug

    Standard medical therapy will include dietary restriction of sodium, treatment with diuretics, repeated LVP as needed and other supportive care. Patients on non-selective beta blockers will continue to do so with dose modifications/withdrawal as per Baveno VI guidelines.

Study groups in NCT05014594
Study groupRoleWhat they receive
Group A (Dapaglifozin)Active comparatorGroup A will receive oral Dapaglifozin (10 mg/day) along with standard medical therapy for 6 months
Receives: Drug: Dapagliflozin (10Mg Tab) along with standard medical therapy
Group B (Placebo)Placebo comparatorGroup B will receive placebo of Dapaglifozin along with standard medical therapy for 6 months
Receives: Drug: Placebo of dapaglifozin along with standard medical therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. control of ascites at 6-months

    Control of ascites will be defined as follows-

    • Complete response will be total absence of ascites.
    • Partial response as presence of ascites not requiring paracentesis
    • Non response will be defined as persistence of severe ascites requiring paracentesis.

    Measured: 6 months

Secondary outcomes (20)

  1. Change in eGFR measured by MDRD-6 at 3 months and 6 months

    eGFR will be measured by MDRD-6 formula

    Measured: 6 months

  2. Change in urine output at 2-weeks, 3-months and 6-months

    Change in 24-hour urine output (ml) at 6-months

    Measured: 6-months

  3. Change in serum sodium (mEq/l) at 2-weeks, 3-months and 6 months

    Change in serum sodium (mEq/l)

    Measured: 6 months

  4. Change in 24-hours urinary sodium (mEq) at 2 weeks, 3 months and 6 months

    Change in 24-hours urinary sodium (mEq)

    Measured: 6 months

  5. Change in HbA1c at 3 and 6 months

    Change in HbA1c

    Measured: 6 months

  6. Change in Child-Turcotte-Pugh (CTP) score at 3 months and 6 months

    Change in CTP score. The CTP score incorporates the variables of serum bilirubin, albumin, prothrombin time-INR, grade of ascites and hepatic encephalopathy. The score ranges from 5-15 and a higher score portends a worse prognosis

    Measured: 6 months

  7. Change in model for end stage liver disease (MELD) score at 3 months and 6 months

    Change in MELD score. The MELD score incorporates the variables of serum bilirubin, creatinine and Internation Normalised Ratio (INR). Higher MELD score indicates worse prognosis

    Measured: 6 months

  8. Incidence of spontaneous bacterial peritonitis (SBP), urinary tract infection (UTI) and other infections

    The diagnosis of SBP will be based on neutrophil count in ascitic fluid of >250/mm3 as determined by microscopy and positive ascitic fluid culture or >250 /mm3 with negative culture called as culture negative neutrocytic ascites.Other infections will be diagnosed as per CDC criteria.

    Measured: 6 months

  9. Incidence of overt hepatic encephalopathy over 6-months

    Over hepatic encephalopathy (HE) will be defined as grade II or higher HE as per the West haven classification

    Measured: 6 months

  10. Incidence of acute kidney injury over 6-months

    Acute kidney injury will be defined as per the International Club of Ascites criteria

    Measured: 6 months

  11. Incidence of Hyponatremia (serum sodium <130 meq/L), hypokalemia (Serum potassium < 3.5 meq/L), hyperkalemia (Serum potassium >6meq/L) over 6-months.

    Hyponatremia: serum sodium <130 meq/L hypokalemia: serum potassium < 3.5 meq/L hyperkalemia: serum potassium >6meq/L)

    Measured: 6 months

  12. Incidence of skeletal fractures over 6-months

    Incidence of skeletal fractures over 6-months

    Measured: 6 months

  13. Change in bone densitometry as assessed by DEXA at 6-months

    Bone densitometry will be assessed by DEXA

    Measured: 6 months

  14. Incidence of diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic coma over 6-months

    Incidence of diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic coma over 6-months

    Measured: 6 months

  15. Incidence of hepatocellular carcinoma over 6-months

    Hepatocellular carcinoma will be diagnosed based on imaging findings and AFP

    Measured: 6 months

  16. Changes in plasma renin activity and aldosterone levels at 6- months

    Changes in plasma renin activity (ng/ml/hr) and aldosterone (ng/dL) levels at 6- months

    Measured: 6 months

  17. Frequency and volume of LVP over 6-months.

    Frequency and volume of ascitic fluid removed (in litres) over 6-months.

    Measured: 6 months

  18. Survival at 6-months

    Survival at 6-months after start of therapy

    Measured: Survival at 6-months

  19. Safety of dapaglifozin as assessed by adverse effects

    Safety of dapaglifozin as assessed by adverse effects

    Measured: 6 months

  20. Renal resistive index at 6 months

    Renal resistive index will be measured using ultrasound doppler interrogation of intrarenal arteries using formula (peak systolic velocity - end-diastolic velocity) / peak systolic velocity

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2021
  2. Study start3 Sep 2021
  3. Primary completion19 May 2022 (estimated)
  4. Study completion19 May 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05014594
Sponsor's protocol ID
Dapa recurrent ascites
Status last verified
Sep 2021
First submitted
14 Aug 2021
Last updated
5 Sep 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Singh V, De A, Aggrawal R, Singh A, Charak S, Bhagat N. Safety and Efficacy of Dapagliflozin in Recurrent Ascites: A Pilot Study. Dig Dis Sci. 2025 Feb;70(2):835-842. doi: 10.1007/s10620-024-08667-4. Epub 2024 Oct 9.

    PubMed 39384712

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dapagliflozin (10Mg Tab) along with standard medical therapy in people with Cirrhosis and Ascites Hepatic, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Virendra Singh, MD,DM,FASGE (0172-275-6338, virendrasingh100@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

control of ascites at 6-months (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05014594, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in